To continue the systematic assays of new narcotic analgesic compounds for their agonist and antagonist activities. To develop an in vitro method which may be used for the prediction of the absence or presence of physical dependence capacity in new narcotic analgesic compounds. This method depends on the differences in the responses of the guinea-pig ileum and the mouse vas deferens to compounds with high antinociceptive potency but with no antagonist activity and no physical dependence capacity. Such compounds also require more naloxone for antagonism than agonists with high physical dependence. To analyse the mechanisms of the differential behavior of the guinea-pig ileum and mouse vas deferens by comparing pharmacological responses to compounds with their affinities to opiate binding sites in these two models. To develop accurate assay techniques for enkephalin, an endogenous peptide with morphine-like actions, in particular immunoassay and immunofluorescent methods for cytological identification. To use these methods for the study of synthesis, storage and metabolism of enkephalin with a view to developing drugs aimed at these systems. To compare the structure-activity relationships of peptides having opiate agonist and antagonist activities with those of narcotic analgesics. To study the role of the interaction between endogenous enkephalin and exogenous narcotic analgesics in the development of tolerance and dependence. To study the mode of action of narcotic analgesics and enkephalin by intracellular recording from morphine-sensitive neurones in the central and peripheral nervous system. To continue with the analysis of the mechanisms involved in the morphine-sensitive release of transmitter from the myenteric plexus and the mouse vas deferens.